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【结 构 式】 
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【分子编号】17374 【品名】ethyl (4R,5S,7S,8S,10R)-7-formyl-8-methoxy-2,2,10-trimethyl-1,3,6-trioxaspiro[4.5]decane-4-carboxylate 【CA登记号】 |
【 分 子 式 】C15H24O7 【 分 子 量 】316.35136 【元素组成】C 56.95% H 7.65% O 35.4% |
合成路线1
该中间体在本合成路线中的序号：(VI)The completion of the total synthesis of FK-506, starting with the key intermediate C16-C34 fragment obtained as described in Tetrahedron 1997, 53(39): 13221, has been presented: 1) The silyl ether (I) was partially deprotected with tetrabutylammonium fluoride (TBAF) in THF giving the diol (II), which is selectively tosylated with tosyl chloride at the primary OH group yielding the monotosylate (III). The protection of the secondary alcohol of (III) with triethylsilyl chloride (TES-Cl) affords the protected tosylate (IV), which by treatment with lithium iodide and sodium benzenesulfinate is converted into the sulfone (V). The condensation of (V) with aldehyde (VI) by means of butyllithium followed by Dess-Martin oxidation gives a nonisolated ketosulfone intermediate, which was treated with tri-butyltin hydride and azobis(isobutyronitrile) (AIBN) yielding ketone (VII).
| 【1】 Liu, L.B.; Roper, T.D.; Gleason, J.L.; Ireland, R.E.; Total synthesis of FK-506. 2. Completion of the synthesis. Tetrahedron 1997, 53, 39, 13257. |
| 【2】 Liu, L.B.; Roper, T.D.; Ireland, R.E.; Total synthesis of FK-506. 1. Construction of the C16-C34 fragment. Tetrahedron 1997, 53, 39, 13221. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 17369 | (E,3S,4S)-4-[11-((E,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-1-pentenyl)-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-4-yl]-1-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-2-methyl-1-penten-3-ol | C60H92O9Si2 | 详情 | 详情 | |
| (II) | 17370 | (2S,4E)-5-[4-[(1S,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-2-hydroxy-1,3-dimethyl-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-2,4-dimethyl-4-penten-1-ol | C54H78O9Si | 详情 | 详情 | |
| (III) | 17371 | (2S,4E)-5-[4-[(1S,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-2-hydroxy-1,3-dimethyl-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-2,4-dimethyl-4-pentenyl 4-methylbenzenesulfonat | C61H84O11SSi | 详情 | 详情 | |
| (IV) | 17372 | (2S,4E)-5-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-2,4-dimethyl-4-pentenyl 4-methylbe | C67H98O11SSi2 | 详情 | 详情 | |
| (V) | 17373 | (2S,4E)-5-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-2,4-dimethyl-4-pentenyl benzenesul | C66H96O11SSi2 | 详情 | 详情 | |
| (VI) | 17374 | ethyl (4R,5S,7S,8S,10R)-7-formyl-8-methoxy-2,2,10-trimethyl-1,3,6-trioxaspiro[4.5]decane-4-carboxylate | C15H24O7 | 详情 | 详情 | |
| (VII) | 17375 | ethyl (4R,5S,7S,8S,10R)-7-((3S,5E)-6-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethyl-5-hexenoyl)-8-methoxy-2,2,10-trimethyl-1,3,6-trioxaspiro[4.5]decane-4-carboxylate | C75H114O15Si2 | 详情 | 详情 |